Delayed effects of thallium in the rat brain: regional changes in lipid peroxidation and behavioral markers, but moderate alterations in antioxidants, after a single administration.

Thallium (Tl+) toxicity has been related with the generation of reactive oxygen species (ROS) and oxidative stress (OS) in the central nervous system. Since changes in endogenous antioxidant systems might contribute to acute Tl+-induced OS and neurotoxicity, in this study we measured the metal concentration and the levels of lipid peroxidation (LP) in different brain regions (hypothalamus (Ht); cerebellum (Ce); striatum (S); hippocampus (Hc) and frontal cortex (Cx)) in possible correlation with the content of reduced glutathione (GSH), the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and the animal performance in behavioral tests, all evaluated after a single administration of thallium acetate (8 or 16 mg/kg, i.p.) to rats. Seven days after Tl+ administration, the metal was homogeneously and dose-dependently accumulated in all regions evaluated. LP was increased in Ht, Ce and S, while GSH was depleted in S. Cu,Zn-SOD activity was also decreased in Ht and S. All these changes occurred with 16 mg/kg dose and at 7 days after treatment, but not at 1 or 3 days. In addition, Tl+-treated animals exhibited general hypokinesis, but no changes were observed in spatial learning. Our findings suggest that a delayed response of the brain to Tl+ may be the result of its residual levels. Also, despite the regional alterations produced by Tl+ in LP and the limited changes in endogenous antioxidants, there is a correlation between the Tl+-induced oxidative damage and the affected behavioral tasks, suggesting that, although still moderate, Tl+ evokes neurotoxic patterns under the experimental conditions tested.     

Implementing the National Local Public Health System Performance Assessment: evaluation of a readiness process in Kentucky.

The objectives of the study described in this article were to test training and resource materials for preparing Kentucky public health agency staff to lead the National Local Public Health System Performance Assessment and to identify barriers encountered in implementation. Readiness supports provided to five Kentucky district and county health departments that led the system assessment process in 12 counties were evaluated using training pre- and posttests, performance assessment posttests, observations, and interviews. The training and materials provided in this study appeared to be the minimum needed for these Kentucky health departments. Training sequences need to allow time for independent study of assessment processes, and training in using and interpreting the assessment instrument should be included. Partner orientation materials targeted for nonpublic health partners would be useful. In Kentucky, barriers to completing the assessment included questions about its purpose and benefits and the lack of a self-identified local public health system. Formal training of health department staff, committed leadership, and adequate personnel resources can help overcome these barriers. The health departments that brought together system partners for the performance assessment considered it a valuable community-building educational event.     

Expanding the living related donor pool in renal transplantation: use of marginal donors

PURPOSE: In a living related transplantation program it is not always possible to find an ideal donor. Sometimes the only available donor in the family has some benign disease or suboptimal renal anatomy or physiology, or is too old to be accepted and defined as a marginal donor. However, with proper screening the donor pool can be increased by accepting these marginal donors and treating the benign diseases which is beneficial to the donor. We evaluate the outcome of grafts from marginal donors. MATERIALS AND METHODS: From July 1988 to August 1997, 581 live related transplantations were performed. Of the donors 52 were older than 60 years and 34 had associated benign renal or nonrenal anomaly or disease. These donors were accepted after thorough questioning and consultation with family members. The recipients of graft from elderly donors were evaluated for the number of rejections, serum creatinine at last followup and graft survival. RESULTS: Of the recipients 52 received grafts from elderly donors with a mean age of 62.6+/-3.7 years. Mean followup was 34.14+/-0.7 months. The 2 and 5-year actuarial graft survival was 96% and 74%, respectively. Creatinine was normal (less than 1.5) in 37% of recipients and 1.5 to 2.5 mg.% in 46%. The rejection rate in postoperative month 1 was 29%. All donors underwent simultaneous surgery to treat the benign disease, and all did well after surgery. CONCLUSIONS: By accepting these marginal donors a 14.6% increase in the living related donor pool was achieved without compromising recipient or donor safety. Otherwise these recipients would have been forced to undergo unrelated transplantation or be maintained on dialysis, which is particularly difficult in a developing country. Donors with associated disease benefited from cure.     

Childhood obesity increases duration of therapy during severe asthma exacerbations.

OBJECTIVES: Childhood obesity contributes to a wide array of medical conditions, including asthma. There is also increasing evidence in adult patients admitted to the intensive care unit (ICU) that obesity contributes to increased morbidity and to a prolonged length of stay. We hypothesized that obesity is associated with the need for increased duration of therapy in children admitted to the ICU with status asthmaticus. DESIGN: Retrospective cohort study. SETTING: A tertiary pediatric ICU in a university-affiliated children's hospital. PATIENTS: We retrospectively examined data from all children older than 2 yrs admitted to the ICU with status asthmaticus between April 1997 and June 2004. Children were classified as normal weight (<95% weight-for-age percentile) or obese (>95% weight-for-age). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 209 children admitted to the ICU with asthma, 45 (22%) were obese. Compared with children of normal weight, the obese children were older (9.7 +/- 4.4 vs. 8.0 +/- 4.3 yrs, p = .02), more likely to be female (60% vs. 37%, p < .01), and more likely to have been admitted to the ICU previously (40% vs. 20%, p = .01). The obese children also had a statistically significant difference in race (more likely to be Hispanic) and in baseline asthma classification (more likely to have persistent asthma). Despite similar severity of illness at ICU admission, obese children had a significantly longer ICU length of stay (116 +/- 125 hrs vs. 69 +/- 57 hrs, p = .02) and hospital length of stay (9.8 +/- 7.0 vs. 6.5 +/- 3.4 days, p < .01). Obese children also received longer courses of supplemental oxygen, continuous albuterol, and intravenous steroids. CONCLUSIONS: Childhood obesity significantly affects the health of children with asthma. Obese children with status asthmaticus recovered more slowly from an acute exacerbation, even after adjustment for baseline asthma severity and admission severity of illness.     

Oftalmoplejía completa izquierda por metástasis ósea de cáncer de próstata

Prognosis in prostate cancer is determined, in greater part, by the presence of metastases. Bone metastases can occur in any part of the skeleton even, for example, at the base of the skull. We present a case of a 78 year old male who, in December 2001, presented with paralysis of the third cranial nerve. The NMR and CAT scans were normal and circulating levels of PSA were elevated. He was referred to the Urology Service where the treatment guidelines included complete androgen block. Subsequently, he developed retro-orbital pain, divergent strabismus and palpebral ptosis. CAT and NMR indicated a soft tissue mass at the sphenoid level. Treatment was Gamma Knife Radio-surgery. Since August 2004, in conjunction with the latest rise in PSA, the patient's general status deteriorated considerably and he was referred to the Oncology Service. there was an increase in the paralysis of the third, fourth and sixth cranial nerve (complete left ophthalmoplegia) and left-central facial paralysis. Metastases from prostate cancer can be disseminated via the lymphatic or the blood system. Currently, there are more metastases from large-size tumours. Metastases are critical in prostate cancer because of their adverse effect on the patient's survival. Measurements of circulating levels of prostate specific antigen and prostate acid phosphatase are very useful in the clinical diagnosis of the primary tumour, or its metastases.     

SYNTHESIS OF THE RIGID ANALOGUES OF AN SSRI BENZENEPROPANAMINE

Several 1-(substituted phenoxy)-3-{[4-(4-trifluoromethyl) phenoxy] piperidin-1-yl} propan-2-ols (str.II) were prepared in a six-step reaction sequence starting from methylamine and ethyl acrylate and evaluated for antidepressant activity. The compounds were fully characterized by spectral and elemental analyses, and were tested for their effect on gross behavior, antireserpine and anorexigenic activity. No effect was observed on gross behavior and some of them showed fluoxetine like antireserpine and anorexigenic activity.     

Modulatory effect of soy isoflavones on biochemical alterations mediated by TPA in mouse skin model.

Exposure to various carcinogenic agents along with other contributing factors increase the risk of cancer formation. The current study assesses the effect of soy isoflavones on the biochemical events associated with tumor promotion in mouse skin. 12-O-tetradecanoyl phorbol-13-acetate (TPA), a well-known tumor promoter on topical application depletes the reduced glutathione content (GSH) and down regulates the activities of its metabolizing enzyme, glutathione-S-transferase (GST) and the activities of antioxidant enzymes. However, the ornithine decarboxylase (ODC) activity and unscheduled DNA synthesis are elevated on single topical application of TPA to the dorsal cutaneous portions of the mice. Topical applications of soy isoflavones, half-an-hour prior to the application of TPA prevented the induction of ODC activity and DNA synthesis mediated by TPA (p < 0.01). The content of GSH, GST and antioxidant enzymes (p < 0.05) was also recovered significantly by soy isoflavones in a dose dependent manner. Parallel to these effects, pretreatment with the soy isoflavones also reduced hydrogen peroxide (H2O2) content (p < 0.05) at 1.0 and 2.0 microg/0.2 ml vehicle/animal. Therefore, we conclude that soy isoflavones are potentially protective against TPA induced biochemical alterations.     

Chromatin remodelling and DNA repair genes are frequently mutated in endometrioid endometrial carcinoma

In developed countries, endometrial carcinoma is the most common cancer that affects the female genital tract. Endometrial carcinoma is divided into two main histological types, type I or endometrioid and type II or non‐endometrioid, each of which have characteristic, although not exclusive, molecular alterations and mutational profiles. Nevertheless, information about the implication and relevance of some of these genes in this disease is lacking. We sought here to identify new recurrently mutated genes in endometrioid cancers that play a role in tumourigenesis and that influence the clinical outcome. We focused on low‐grade, non‐ultramutated tumours as these tumours have a worse prognosis than the ultramutated POLE‐positive endometrioid endometrial carcinomas (EECs). We performed exome‐sequencing of 11 EECs with matched normal tissue and subsequently validated 15 candidate genes in 76 samples. For the first time, we show that mutations in chromatin remodelling‐related genes (KMT2D, KMT2C, SETD1B and BCOR) and in DNA‐repair‐related genes (BRCA1, BRCA2, RAD50 and CHD4) are frequent in this subtype of endometrial cancer. The alterations to these genes occurred with frequencies ranging from 35.5% for KMT2D to 10.5% for BRCA1 and BCOR, with some showing a tendency toward co‐occurrence (RAD50‐KMT2D and RAD50‐SETD1B). All these genes harboured specific mutational hotspots. In addition, the mutational status of KMT2C, KMT2D and SETD1B helps to predict the degree of myometrial invasion, a critical prognostic feature. These results highlight the possible implication of these genes in this disease, creating opportunities for new therapeutic approaches.